N-methyl-2-pyrrolidone → HCID 67112284, compound

HRID 2088900Notes

Reaction equation

HRID 2088900 reaction equation
Cl[C:2]1[C:3]2[C@H:11]([CH3:12])[CH2:10][C:9](=[O:13])[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.Cl.Cl.Cl.[CH2:17]([C:21]1[N:22]=[C:23]([CH:33]2[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)[N:24]([CH2:26][CH2:27][N:28]2[CH2:32][CH2:31][CH2:30][CH2:29]2)[CH:25]=1)[CH:18]([CH3:20])[CH3:19].CN1CCCC1=O.C(N(C(C)C)CC)(C)C>O>[CH2:17]([C:21]1[N:22]=[C:23]([CH:33]2[CH2:38][CH2:37][N:36]([C:2]3[C:3]4[C@H:11]([CH3:12])[CH2:10][C:9](=[O:13])[NH:8][C:4]=4[N:5]=[CH:6][N:7]=3)[CH2:35][CH2:34]2)[N:24]([CH2:26][CH2:27][N:28]2[CH2:29][CH2:30][CH2:31][CH2:32]2)[CH:25]=1)[CH:18]([CH3:20])[CH3:19]

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 67113241HCID 67113241, compoundHCID 86666575(R)-4-chloro-5-methyl-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one

Product 1

HCID 67112284HCID 67112284, compoundYield 23.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
200 °C

Procedure

Add (R)-4-chloro-5-methyl-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one (0.23 g, 1.18 mmol), 4-(4-isobutyl-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-2-yl)piperidine trihydrochloride (0.64 g, 1.3 eq), N-methylpyrrolidinone (10 mL) and diisopropylethylamine (1.65 mL, 8.0 eq) in a microwave tube. Seal with crimp cap. Heat in a microwave reactor at 200° C. for 40 minutes. Dilute the reaction mixture with water and extract with ethyl acetate. Wash with saturated aqueous sodium chloride. Dry the organics over anhydrous magnesium sulfate, filter, and concentrate in vacuo. Purify by normal phase chromatography, eluting with hexanes to ethyl acetate to 5% methanol/ethyl acetate to 3% to 5% to 7% to 10% methanol/dichloromethane, to give the title compound (0.13 g, 23%). MS (ES) m/z=466 [M]+.

Workup

  1. customSeal with crimp cap
  2. extractionextract with ethyl acetate
  3. washWash with saturated aqueous sodium chloride
  4. dry with materialDry the organics over anhydrous magnesium sulfate
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify by normal phase chromatography
  8. washeluting with hexanes to ethyl acetate to 5% methanol/ethyl acetate to 3% to 5% to 7% to 10% methanol/dichloromethane

Sources & evidence

ORD record
ord-d2eb2ed45a9b4208a805ebca16a61410
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

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